Mesenchymal-specific deletion of C/EBPβ suppresses pulmonary fibrosis.

The CCAAT/enhancer-binding protein β (C/EBPβ) regulates a variety of factors and cellular responses associated with pulmonary fibrosis. To distinguish its role in the mesenchyme from that in other compartments, the effects of mesenchymal-specific deletion of C/EBPβ on pulmonary fibrosis was examined. Crossing of mice with the floxed C/EBPβ gene with α2(I) collagen enhancer-CreER(T)-bearing mice successfully generated progeny with a conditional knockout (CKO) of C/EBPβ in collagen I-expressing ("mesenchymal") cells only on treatment with tamoxifen (C/EBPβ CKO).

Mining biological information from 3D short time-series gene expression data: the OPTricluster algorithm.

Background: Nowadays, it is possible to collect expression levels of a set of genes from a set of biological samples during a series of time points. Such data have three dimensions: gene-sample-time (GST). Thus they are called 3D microarray gene expression data.

Recent developments in myofibroblast biology: paradigms for connective tissue remodeling.

The discovery of the myofibroblast has opened new perspectives for the comprehension of the biological mechanisms involved in wound healing and fibrotic diseases. In recent years, many advances have been made in understanding important aspects of myofibroblast basic biological characteristics. This review summarizes such advances in several fields, such as the following: i) force production by the myofibroblast and mechanisms of connective tissue remodeling; ii) factors controlling the expression of α-smooth muscle actin, the most used marker of myofibroblastic phenotype and, more important, involved in force generation by the myofibroblast; and iii) factors affecting genesis of the myofibroblast and its differentiation from precursor cells, in particular epigenetic factors, such as DNA methylation, microRNAs, and histone modification.

Evaluating the link between self-assembled mesophase structure and drug release.

Lipid-based liquid crystalline materials are of increasing interest for use as drug delivery systems. The intricate nanostructure of the reversed bicontinuous cubic (V(2)) and inverse hexagonal (H(2)) liquid crystal matrices have been shown to provide diffusion controlled release of actives of varying size and polarity. In this study, we extend the understanding of release to other self-assembled phases, the micellar cubic phase (I(2)) and inverse micelles (L(2)).

Adjunct mirtazapine for negative symptoms of schizophrenia.

Negative symptoms of schizophrenia are characterized by affective flattening, alogia, avolition, and anhedonia and are often nonresponsive to antipsychotic therapy. Because negative symptoms are predictive of poor occupational and social functioning, as well as poor global outcomes, numerous studies evaluating adjunct therapy to antipsychotics have been conducted. This review focuses on the use of the antidepressant mirtazapine as adjunct therapy to antipsychotics for the treatment of negative symptoms of schizophrenia.

Three-dimensional reconstruction of serial mouse brain sections: solution for flattening high-resolution large-scale mosaics.

Recent advances in high-throughput technology facilitate massive data collection and sharing, enabling neuroscientists to explore the brain across a large range of spatial scales. One such form of high-throughput data collection is the construction of large-scale mosaic volumes using light microscopy (Chow et al., 2006; Price et al.

FIZZ2/RELM-β induction and role in pulmonary fibrosis.

Found in inflammatory zone (FIZZ) 2, also known as resistin-like molecule (RELM)-β, belongs to a novel cysteine-rich secreted protein family named FIZZ/RELM. Its function is unclear, but a closely related family member, FIZZ1, has profibrotic activities. The human ortholog of rodent FIZZ1 has not been identified, but human FIZZ2 has significant sequence homology to both rodent FIZZ2 (59%) and FIZZ1 (50%).

Physical activity and neural correlates of aging: a combined TMS/fMRI study.

Aerobic exercise has been suggested to ameliorate aging-related decline in humans. Recently, evidence has indicated chronological aging is associated with decreases in measures of interhemispheric inhibition during unimanual movements, but that such decreases may be mitigated by long-term physical fitness. The present study investigated measures of ipsilateral (right) primary motor cortex activity during right-hand movements using functional magnetic resonance imaging and transcranial magnetic stimulation (TMS).

Essential role of MeCP2 in the regulation of myofibroblast differentiation during pulmonary fibrosis.

DNA methylation is a key mechanism for repression of gene expression, including that of α-smooth muscle actin (α-SMA) gene expression in fibroblasts. However, the trans-acting factors that interact with the methylated α-SMA gene to regulate its expression have not been identified. Using gel shift and chromatin immunoprecipitation (ChIP) assays, methyl CpG binding protein 2 (MeCP2) was shown to bind to the α-SMA gene.

RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer.

Purpose: This phase III study compared the efficacy and safety of bevacizumab (BV) when combined with several standard chemotherapy regimens versus those regimens alone for first-line treatment of patients with human epidermal growth factor receptor 2-negative metastatic breast cancer.

Patients And Methods: Patients were randomly assigned in 2:1 ratio to chemotherapy plus BV or chemotherapy plus placebo. Before random assignment, investigators chose capecitabine (Cape; 2,000 mg/m(2) for 14 days), taxane (Tax) -based (nab-paclitaxel 260 mg/m(2), docetaxel 75 or 100 mg/m(2)), or anthracycline (Anthra) -based (doxorubicin or epirubicin combinations [doxorubicin/cyclophosphamide, epirubicin/cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide, or fluorouracil/doxorubicin/cyclophosphamide]) chemotherapy administered every 3 weeks.

Prolonged sinus pauses with hydromorphone in the absence of cardiac conduction disease.

A 49-year-old male had open sigmoid colectomy with colorectal anastomosis for sigmoid diverticulitis. The patient was given patient-controlled analgesia (PCA) hydromorphone and subsequently developed bradycardia with prolonged sinus pauses up to 7.1 seconds.

Characterization of vascular strain during in-vitro angioplasty with high-resolution ultrasound speckle tracking.

Background: Ultrasound elasticity imaging provides biomechanical and elastic properties of vascular tissue, with the potential to distinguish between tissue motion and tissue strain. To validate the ability of ultrasound elasticity imaging to predict structurally defined physical changes in tissue, strain measurement patterns during angioplasty in four bovine carotid artery pathology samples were compared to the measured physical characteristics of the tissue specimens.

Methods: Using computational image-processing techniques, the circumferences of each bovine artery specimen were obtained from ultrasound and pathologic data.

Phase II trial of anastrozole plus goserelin in the treatment of hormone receptor-positive, metastatic carcinoma of the breast in premenopausal women.

Purpose: To explore the antitumor activity of the aromatase inhibitor, anastrozole, in the treatment of premenopausal women with hormone receptor-positive, metastatic breast cancer who have been rendered functionally postmenopausal with the use of the luteinizing hormone-releasing hormone agonist, goserelin.

Patients And Methods: Premenopausal women with estrogen and/or progesterone receptor-positive, metastatic or recurrent breast cancer were enrolled in this prospective, single-arm, multicenter phase II trial. Patients were treated with goserelin 3.

Epigenetic regulation of myofibroblast differentiation by DNA methylation.

DNA methylation, a key mechanism of repressing gene expression, is of particular relevance in controlling development and cell differentiation. We analyzed the extent and regulation of DNA methylation of the alpha-smooth muscle actin (alpha-SMA) gene to elucidate its potential role in myofibroblast differentiation. These experiments revealed the presence of three CpG islands that were methylated at different levels in fibroblasts, myofibroblasts, and alveolar epithelial type II cells.

GOAL: a software tool for assessing biological significance of genes groups.

Background: Modern high throughput experimental techniques such as DNA microarrays often result in large lists of genes. Computational biology tools such as clustering are then used to group together genes based on their similarity in expression profiles. Genes in each group are probably functionally related.

Symptomatic bradycardia with oral aripiprazole and oral ziprasidone.

Objective: To describe the case of a patient who developed symptomatic bradycardia upon initiation of oral ziprasidone and later with oral aripiprazole, both of which resolved shortly after discontinuation of therapy.

Case Summary: An 18-year-old female with bipolar disorder was started on oral ziprasidone 80 mg at night and the dose was subsequently increased to 120 mg for management of acute mania and delusions. The patient developed symptomatic bradycardia (heart rate 31-35 beats/min), which resolved after ziprasidone was decreased to 80 mg.

A multi-strategy approach to informative gene identification from gene expression data.

An unsupervised multi-strategy approach has been developed to identify informative genes from high throughput genomic data. Several statistical methods have been used in the field to identify differentially expressed genes. Since different methods generate different lists of genes, it is very challenging to determine the most reliable gene list and the appropriate method.

Anti-tumor activity of stability-engineered IgG-like bispecific antibodies targeting TRAIL-R2 and LTbetaR.

Bispecific antibodies (BsAbs) represent an emerging class of biologics that achieve dual targeting with a single agent. Recombinant DNA technologies have facilitated a variety of creative bispecific designs with many promising therapeutic applications; however, practical methods for producing high quality BsAbs that have good product stability, long serum half-life, straightforward purification, and scalable production have largely been limiting. Here we describe a protein-engineering approach for producing stable, scalable tetravalent IgG-like BsAbs.

Serial reconstruction and montaging from large-field electron microscope tomograms.

Electron microscope tomography [1] has been proven as an essential technique for imaging the structure of cells beyond the range of the light microscope down to the molecular level. However, because of the extreme difference in spatial scales, there is a large gap to be bridged between light and electron microscopy. Various techniques have been developed, including increasing size of the sensor arrays, serial sectioning and montaging.

Effects of motexafin gadolinium in a phase II trial in refractory chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) cells are susceptible to oxidative stress. The expanded porphyrin, motexafin gadolinium (MGd), reacts with intracellular reducing metabolites and protein thiols to generate reactive oxygen species (ROS). A phase II trial administered MGd 5 mg/kg/day IV for 5 days every 3 weeks until disease progression to patients with previously treated CLL and small lymphocytic lymphoma.

Enhanced MR imaging of the shoulder, and sternoclavicular and acromioclavicular joint arthritis in primary hemochromatosis.

Shoulder arthritis is a common feature of hemochromatosis. However, a combination of sternoclavicle (SC) and acromioclavicular (AC) joint involvement associated with shoulder is uncommonly seen. We describe the MR imaging findings of the shoulder and SC and AC joint in a patient with primary hemochromatosis.

Toll-like receptor 9 activation is a key mechanism for the maintenance of chronic lung inflammation.

Rationale: Accumulating evidence supports the hypothesis that the continuous host response to a persistent challenge can polarize the cytokine environment toward a Th2 cytokine phenotype, but the mechanisms responsible for this skewing are not clear.

Objectives: We investigated the role of Toll-like receptor 9 (TLR9) in a Th2-driven pulmonary granulomatous response initiated via the embolization of Schistosoma mansoni eggs to the lungs of mice.

Methods: Mice were intravenously injected with S.

Endothelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis.

The pathological hallmark lesions in idiopathic pulmonary fibrosis are the fibroblastic foci, in which fibroblasts are thought to be involved in the tissue remodeling, matrix deposition, and cross-talk with alveolar epithelium. Recent evidence indicates that some fibroblasts in fibrosis may be derived from bone marrow progenitors as well as from epithelial cells through epithelial-mesenchymal transition. To evaluate whether endothelial cells could represent an additional source for fibroblasts, bleomycin-induced lung fibrosis was established in Tie2-Cre/CAG-CAT-LacZ double-transgenic mice, in which LacZ was stably expressed in pan-endothelial cells.

Erythromycin-induced CXCR4 expression on microvascular endothelial cells.

Although stromal-derived factor-1 (SDF-1) via its cognate receptor CXCR4 is assumed to play a critical role in migration of endothelial cells during new vessel formation after tissue injury, CXCR4 expression on endothelial cells is strictly regulated. Erythromycin (EM), a 14-membered ring macrolide, has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases. However, the effects of EM on endothelial cells and especially their expression of CXCR4 have not been fully evaluated.